Microdrop

ABSTRACT

The invention is a system ( 1 ), which dispenses a microliter dose of a liquid ( 6 ) or medicament. A flow channel ( 33 ) holds a dose of the liquid. A bubble ( 7 ) is located within the dose. A typical dose can be  3  microliters, or  5  microliters, including others. The invention is intended to be utilized in conjunction with gasdrop technology. a method of dispensing the dosage includes: injecting air into the inlet ( 4 ). this causes the dose to be ejected through the outlet ( 5 ). The accuracy of the dose is plus or minus  0.5  microliters.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] not applicable

STATEMENT OF FEDERALLY SPONSORED RESEARCH/DEVELOPMENT

[0002] not applicable

REFERENCE TO A MICROFICHE APPENDIX

[0003] not applicable

BACKGROUND OF THE INVENTION

[0004] There are many devices, designed to dispense microliter dosages of liquid or medicament. For example, in Laibovitz, et al., U.S. Pat. No. 5,997,518, an apparatus and method for delivery of small volumes of liquid is disclosed. This device utilizes a jet pump to dispense a dosage having the form of many droplets. In column 14, Table 1, experimental results of Laibovitz include:

[0005] experiment No. 1: Average 2.0 microliter, Standard Deviation 0.5, Max 2.9 microliter, Min 1.3 microliter.

[0006] experiment No. 2: Average 6.0 microliter, Standard Deviation 0.6, Max 7.1 microliter, Min 4.7 microliter.

[0007] In Cohen, et al, U.S. Pat. No. 5,881,956, a microdispensing ophthalmic pump is disclosed. This device dispenses a dose of approximately 5 microliters. The accuracy of the dosage for this device is unknown.

[0008] In Coffelt, Jr, U.S. Pat. No. 6,206,297, there is shown, devices and methods of manufacturing a gasdrop. These devices are typically a dual chamber device. The accuracy of the devices, for microliter dosages, is unknown.

[0009] Therefor the present invention will be greatly appreciated for delivering microliter dosages of a liquid or medicament. And further, the dosages are accurate to within plus or minus 0.5 microliters.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING

[0010] The invention is further described by reference to the appended drawings taken in conjunction with the following description where:

[0011]FIG. 1 is a perspective sectional view of a microliter dosage system (1).

[0012]FIG. 2 is a front view of an apparatus for dispensing the dosage, which includes: dosage system (1); tube (8); bottle (10).

[0013]FIG. 3 is a front perspective sectional view of a microdrop (12).

[0014]FIG. 4 is a sectional view of the system after beginning injection of air; the liquid having a concave surface at the upstream end of the liquid.

[0015]FIG. 5 is a front sectional view of the system after beginning injection of air; the concave surface of FIG. 2 beginning to form a bubble (14); air injected into bubble (14) at point “B”.

[0016]FIG. 6 is a front sectional view of the system after beginning injection of air; the opening at point “B” (FIG. 3) is closed; a bubble (14); a bubble (7); a microdrop (15) suspended below a surface.

DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention resides in a microliter dosage system, intended to be utilized in conjunction with gasdrop technology. In Coffelt, Jr., U.S. Pat. No. 6,206,297, a gasdrop, devices and methods of manufacturing a gasdrop is disclosed. The accuracy of the gasdrop in '297, in the microliter range, is unknown.

[0018] The present Invention may include a novel drop of liquid. This drop may be a spheroidal ball of liquid enclosing a spheroidal ball of air.

[0019] In Coffelt, Jr., U.S. patent application Ser. No.: 09/706,329, filed Nov. 04, 2000 (abandoned), an apparatus and method for manufacturing a gasdrop is disclosed. The accuracy of the devices in this Application, in the microliter range, is unknown.

[0020] The present invention, a microliter dosage system, includes:

[0021] a flow channel having an inlet, and an outlet;

[0022] a microliter dosage of a liquid disposed within the flow channel;

[0023] a bubble disposed within the liquid.

[0024] Embodiments of the present invention are hereinafter described with reference to the drawings, in which identical or corresponding parts are indicated by the same reference characters or numbers through the several views.

[0025] Referring to FIG. 1, there is shown, a left side perspective sectional view of a microliter dosage system (1). The system is symmetrical, therefore, the right side view is a mirror image of FIG. 1. The system includes a conical tubular wall (2). The longitudinal axis of wall (2) is vertical. The upper end of wall (2) is integrally formed with a horizontal disk shaped wall (3). Wall (2) and wall (3) form a flow channel (33). Wall (3) is formed with a centrally located 0.25 millimeter diameter opening (4).

[0026] The inner diameter of the upstream end of the flow channel (located at wall (3)) is 0.6 millimeters. The downstream end (5) of the flow channel is an annular arcuate surface, and the lowest extremity of this surface is a circle lying in a horizontal plane. The inner diameter of the flow channel (at 1 millimeter above said circle) is 1.4 millimeters. The volume of the flow channel is calculated to be approximately 8.9 microliters. For example, wall (2), wall (3), and opening (4) can be a standard dispensing tip from a 30 milliliter bottle of CLEAR EYES eye drops. The flow channel may have alternate configurations. For example, the flow channel may be cylindrical, 1 millimeter ID and 2 millimeter OD, including others.

[0027] A microliter dosage (6) is disposed within the flow channel as shown in FIG. 1. The lower surface of the dosage is indicated by the arcuate line at point “A”. The dosage can be TIMOLOL 0.5% , TIMOLOL 0.3%, CLEAR EYES, VISINE, or water, including others. TIMOLOL is a product manufactured by Bausch & Lomb Pharmaceuticals, Inc. Tampa, Fla. 33637. CLEAR EYES is a product manufactured by Abbot Laboratories, Columbus, Ohio 43215. VISINE is a product manufactured by Pfizer Inc. New York, N.Y. 10017. The dosage is inherently in a static state (no motion). The dosage shown in FIG. 1 is 5 microliters.

[0028] A ball of gas (bubble) (7) is centrally located in the dosage. Bubble (7) contains 2 microliters of a gas. The thickness of the liquid wall (between the bubble and wall (2) in inherently predetermined. Alternate volumes and quantities of bubble (7) can be empirically determined.

[0029] A method of manufacturing the system includes:

[0030] (1.) with the longitudinal axis of the flow channel horizontal: inserting a syringe through the outlet; locating the tip of the needle near wall (3); injecting dosage;

[0031] (2.) inserting a syringe though the outlet; placing the tip of the needle near the center of the dosage; injecting a gas into the dosage.

[0032] Obviously there are variations of the above method. For example: wall (2) may be adapted with an inlet near wall (3), and an inlet near the center of the flow channel.

[0033] The flow channel can be any material which holds the dosage in a static state. For example, low density polyethylene, teflon, or vinyl. If plastic, the flow channel can be manufactured standard methods, including injection molding.

[0034] Referring to the above described dosage system, the following is a method, among others, of use.

[0035] The system is fitted to a transparent vinyl tube (8). Tube (8) is 6.3 millimeters OD, and 4.3 millimeters ID, and 15 millimeters length. Wall (3) is located at the end of tube (8). Tube (8) is co-axial with wall (2). An annular leak tight seal (9) rigidly attaches the system to tube (8). For example, seal (9) and subsequent seals can be an epoxy resin.

[0036] The upper end of tube (8) is fitted with a 30 milliliter flexible plastic bottle (10). A 1 millimeter diameter opening (16) is bored through the bottle wall at point “S”. The objective of opening (16) is to remove a possible undesired pressure drop across opening (4) during injection of the dosage and bubble (7). For example, bottle (10) can be a standard 30 milliliter CLEAR EYES bottle. An annular leak tight seal (11) rigidly attaches the bottle to tube (8). The longitudinal axis of the bottle is co-axial with tube (8).

[0037] The dosage and bubble are injected into the flow channel, as described above.

[0038] The bottle is held by a thumb at point “S” and a finger at point “T”. Points “S” and “T” are opposing points on the body of the bottle. These points are the typical points used to dispense a normal (approx 29 microliter) pendant drop of liquid from the unaltered CLEAR EYES bottle. The thumb and finger apply opposing compressive force on the bottle. This compressive force closes opening (16). Alternate methods may be utilized to close opening (16) during compression of the bottle. For all of the above listed solutions (e.g. TIMOLOL), the total displacement of the bottle walls, required to dispense the dosage, is approximately 3 millimeters. The total time required for this displacement is approximately 550 milliseconds. Alternate displacements and collapsing velocities can be empirically determined.

[0039] The above volume reduction of the bottle creates a pressure drop across opening (4). Therefore, the gas disposed in the bottle is injected into the flow channel via opening (4) in the direction shown by the vertical arrow in FIG. 1.

[0040] This gas flow ejects the dosage from the flow channel through the outlet. While holding the dispenser above a target, the dosage will fall vertically upon the target.

[0041] The configuration of the dosage, after ejection is inherently predetermined. This configuration is observed to be identical for each trial. For dosages between approximately 7 microliters and approximately 9 microliters, the configuration of the dosage is observed to be as shown in FIGS. 4, 5 and 6. For example: a 8 microliter dosage is a microgasdrop (microdrop) (15) as shown in FIG. 6. At this time, the configuration of the dosage, between approximately 3 microliters and approximately 7 microliters, after ejection, is unknown.

[0042] Given the above parameters, there are only 4 possible configurations as follows:

[0043] (1.) the dosage is a spheroidal drop containing no bubble (droplet),

[0044] (2.) the dosage is a ball of liquid enclosing one bubble (microdrop (12)),

[0045] (3.) the dosage is one thin liquid wall enclosing more than one bubble (microgasdrop or microdrop).

[0046] (4.) the dosage is a ball of liquid enclosing at least 2 compartments; and each compartment encloses a gas (microdrop (15)).

[0047] FIGS. 3 shows a possible configuration of a 3 microliter dosage. This configuration is a spheroidal ball of liquid (12) enclosing a ball of gas (7).

[0048]FIG. 4, FIG. 5, and FIG. 6 show a possible sequence of events which dispense the dosage in the form a microdrop (15). In FIG. 4, the upper surface of the dosage becomes concave. In FIG. 5, the concave surface of the liquid begins to form a bubble, having an opening at point “B”. In FIG. 6, the opening at point “B” closes, forming a bubble (14). Therefore, the combination of dosage (6), bubble (14), and bubble (7) forms a microgasdrop (microdrop) (15).

[0049] As described in '907, the gasdrop comprises a cluster of contiguous bubbles. The cluster is formed of one thin continuous liquid wall.

[0050] Inherent properties of the gasdrop include:

[0051] (1.) contain a particular mass of liquid, which is equal to the mass of a normal solid drop, or

[0052] (2.) contain a particular mass of liquid, which is less than the mass of a normal solid drop, or

[0053] (3.) contain a particular mass of liquid, which is greater than the mass of a normal solid drop, and:

[0054] (a.) contain a particular mass of gas;

[0055] (b.) reduced impact force per square unit of area;

[0056] (c.) form a particular overall size;

[0057] (d.) ability to exist in a static state contiguous with a surface, and gravitationally become detached from the surface;

[0058] (e.) ability to exist in a dynamic state;

[0059] (f.) ability to contact a surface at low velocities.

[0060] The following experiments A to D, were executed utilizing the above described method and dispenser. The equipment utilized in these experiments is as follows:

[0061] (1.) Prototype “P1”. This prototype has the form of the dispenser as shown and described above in FIG. 2. The flow channel (3), and opening (4) is provided by a standard dispensing tip from CLEAR EYES eye drop bottle. The bottle (10) is a standard flexible plastic 30 milliliter CLEAR EYES eye drop bottle.

[0062] (2.) dosage solution as noted.

[0063] (3.) standard 1 cc syringe, 29 gauge (12.7 mm) needle manufactured by Becton Dickinson, Franklin Lakes, N.J. 07417 US. A #8-32 nut is rigidly attached co-axial with the plunger. A 5 centimeter diameter wheel is rigidly attached (co-axial) to a #8-32 screw. The wheel is marked at 30 degree increments. The markings are located at the OD of the wheel. The objective of the screw is to displace the plunger. The objective of the wheel is to measure the rotation of the screw. The end of the screw is milled to a conical shape having a diameter of 0.3 millimeters at the end. A thin sheet of steel is rigidly attached to the end of the plastic plunger. Prior to attaching, a centrally located depression is formed on the sheet of steel. This depression is 0.5 millimeters diameter. The objective of the depression is to maintain the location of the screw on the plunger. The screw is placed on the nut. This syringe is used to inject the liquid. Calculations indicate a 27 degree rotation dispenses 1 microliter

[0064] (4.) The syringe described in No. 3 above. This syringe is used to inject air.

[0065] (5.) holding fixture “C” for the air syringe (fixed location).

[0066] (6.) holding fixture “D” for Prototype “P1” (moveable). These holding fixtures maintain the needle co-axial with the flow channel.

[0067] (7.) magnifying glass, 90 millimeter diameter, approx 5 times power.

[0068] (8.) Scale, 100 divisions per inch, No. 305 R, manufactured by L. S. Starrett, Athol, Mass. US.

[0069] The procedure for experiments A to D include the following steps:

[0070] (1.) For solution, insert needle (syringe is hand held) into the flow channel (via the outlet of the flow channel), locate the tip of the needle near wall (3), rotate wheel, wait 12 seconds, remove needle, record delta AL (angular rotation of the wheel for solution). NOTE: It takes approximately 70 seconds to eject the entire quantity of solution. And the residual liquid remaining on the needle after each trial is 0.5 microliters for delta AL between 90 degrees and 210 degrees; the residual liquid remaining on the needle is 0.2 microliters for delta AL between 30 degrees and 60 degrees.

[0071] (2.) For air, (while holding fixture “D” only) insert needle (syringe is on fixture “C” and prototype “P1” is on fixture “D”) into the flow channel (via the outlet of the flow channel), locate the tip on the needle near the center of the dosage, rotate wheel, wait approx 5 seconds, air is injected into the dosage, a bubble (7) is located near the center of the dosage, while holding fixture “D” only: remove the needle. Record delta AA (quantity of rotation of wheel (for air) in degrees. Note: The longitudinal axis of the needle, and the longitudinal axis of the flow channel are horizontal for steps 1 and 2. For approximately 1000 trials, the location of the dosage and bubble were measured with the above described scale and magnifying glass.

[0072] (3.) While holding fixture “D” only: rotate fixture “D” such that the longitudinal axis of the flow channel is vertical. Observe configuration of dosage.

[0073] (4.) compress bottle walls at points “S” and “T” a total distance of approximately 3 millimeters. This displacement occurs within approximately 550 milliseconds. a possible time includes approximately 900 milliseconds.

[0074] (5.) observe output, and record data.

[0075] In the following experiments:

[0076] delta AL is the quantity of rotation of the wheel (for solution), in degrees. delta AA is the quantity of rotation of the wheel (for air), in degrees. And the dosage is the actual quantity of liquid injected into the flow channel.

[0077] EXPERIMENT A: The following is results utilizing TIMOLOL 0.3%, delta AL=90 degrees, dosage=3 microliters, delta AA=60 degrees, bubble (7)=2 microliters, air temperature at #1 is 27.0 C. and at #21 is 24.5 C., the average total time per trial is 150 seconds (this time includes the time required to record data): MICRODROP MICRODROP TRIAL # DIAMETER TRIAL # DIAMETER 1 1.3 mm 11 overspray only 2 1.3 mm 12 1.3 mm 3 1.3 mm 13 1.3 mm 4 1.3 mm 14 1.3 mm 5 1.3 mm 15 overspray only 6 1.3 mm & overspray 16 overspray only 7 1.3 mm 17 1.3 mm 8 1.3 mm 18 overspray only 9 overspray only 19 1.3 mm 10 1.3 mm 20 1.3 mm 21 1.3 mm

[0078] NOTE: 4 trials were executed (prior to experiment D) with prototype “P1” utilizing TIMOLOL 0.5%, results:

[0079] Trials 1 and 2: dosage=3 microliters, bubble (7)=2 microliters, bubble (7) was located at the upstream end of the dosage. Trials 1 and 2 dispensed a microdrop/1.4 mm diameter.

[0080] Trial 3: dosage=4 microliters, quantity 2 bubbles (7) 1 microliter each, bubbles are centrally located in the dosage. Trials 3 dispensed a microdrop/1.8 mm diameter.

[0081] Trial 4: dosage=4 microliters, quantity 3 bubbles (7), bubble (7)=0.5 microliters located near upstream end, bubble (7)=1 microliter located midstream, third bubble (7)=0.5 microliters located near downstream end. Trail 4 dispensed a microdrop/2 millimeters diameter.

[0082] For these trials 1 to 4, there was excessive residue in the flow channel, and this is likely undesirable, therefore no further experiments were executed with 0.5% solution.

[0083] EXPERIMENT B: The following is results utilizing CLEAR EYES liquid, delta AL=90 degrees, dosage=3 microliters, delta AA =60 degrees, bubble (7)=2 microliters, air temperature at #1 is 27.2 C., the average total time per trial is 270 seconds: MICRODROP MICRODROP TRIAL # DIAMETER TRIAL # DIAMETER 1 1.2 mm 10 1.2 mm 2 1.2 mm 11 1.2 mm 3 1.2 mm 12 1.2 mm 4 1.2 mm 13 1.2 mm 5 1.2 mm 14 1.2 mm 6 1.2 mm 15 1.2 mm 7 1.2 mm 16 1.2 mm 8 1.2 mm 17 1.2 mm 9 1.2 mm 18 1.2 mm

[0084] EXPERIMENT C: The following is results utilizing CLEAR EYES liquid, delta AL=150 degrees, dosage=5 microliters, delta AA=60 degrees, bubble (7)=2 microliters, air temperature at #1 is 26.5 C. and at #26 is 27.0 C, the average total time per trail is 122 seconds: MICRODROP MICRODROP TRIAL # DIAMETER TRIAL # DIAMETER 1 1.3 mm & overspray 14 1.3 mm 2 1.3 mm 15 1.3 mm 3 1.3 mm 16 1.3 mm 4 1.3 mm 17 1.3 mm 5 1.3 mm & overspray 18 1.3 mm 6 1.3 mm & overspray 19 1.3 mm 7 1.3 mm 20 1.3 mm 8 1.3 mm 21 1.3 mm & overspray 9 1.3 mm & overspray 22 1.3 mm 10 1.3 mm 23 1.3 mm & overspray 11 1.3 mm 24 1.3 mm 12 1.3 mm 25 1.3 mm 13 1.3 mm 26 1.3 mm

[0085] EXPERIMENT D: The following is results utilizing SPARKLETS distilled drinking water. SPARKLETS is a product manufactured by Danone Waters of North America, Stamford, Conn. 06902 US, delta AL=90 degrees, dosage=3 microliters, delta AA=60 degrees, (7)=2 microliters, the air temperature at #1 is 27.0 C. and at #17 is 25.0 C., the average total time per trial is 133 seconds: MICRODROP MICRODROP TRIAL # DIAMETER TRIAL # DIAMETER 1 1.2 mm 10 1.2 mm 2 1.2 mm 11 overspray only 3 1.2 mm 12 overspray only 4 1.2 mm 13 overspray only 5 1.2 mm 14 1.2 mm 6 overspray only 15 overspray only 7 1.2 mm 16 overspray only 8 1.2 mm 17 1.2 mm 9 1.2 mm

[0086] NOTE: this experiment includes trials #18 to 23, with a dosage=4 microliters, bubble (7)=2 microliters, results: 4 trials dispensed a microdrop/1.2 mm dia. 2 trials dispensed overspray only.

[0087] Additional experiments with “P1” and the above solutions and parameters dispensed microdrops having a dosage of 7, 8, and 9 microliters. The results for these 7 to 9 microliter dosages are similar to the above results. Also experiments were executed with a cylindrical flow channel, 1 millimeter ID, 2 millimeter OD, 13 millimeter length, high density polyethylene. The results with this cylindrical flow channel (for dosages between 3 to 5 microliters) are similar to the above results. The syringe and dispenser were flushed 20 times with SPARKLETS distilled water, prior to experiment D.

[0088] All of the above dimensions of the diameter of the microdrop are estimates based on visual observation. For example, the configuration of the microdrop appears to be identical for each trial, therefore, the diameter of each microdrop appears to be identical, for each trial. The accuracy of the dosage is calculated to be plus or minus 0.5 microliters. The same person executed all trials.

[0089] There are variations of the above describe system, which will dispense a microdrop. Several of the variations are described in experiment A. For example, there may be two or three bubbles (7), the flow channel may be cylindrical having a 1 millimeter ID, there may be alternate collapsing velocities, alternate solutions, alternate gases, alternate mechanical methods of injecting the dosage, bubble (7). Opening (4) may have alternate diameters.

[0090] The bottle compressed by hand may be replaced by a mechanical apparatus. For example, a syringe adapted with a spring actuated piston, including others.

[0091] Obviously, many modifications and variations of the present invention, as hereinbefore set forth, may be made without departing from the spirit and scope thereof, and therefor, only such limitations should be imposed as are indicated by the appended claims. 

I claim:
 1. A microliter dosage system comprising: a chamber having an inlet and an outlet; a dosage of liquid disposed within said flow channel; at least one bubble disposed within said dosage.
 2. The system according to claim 1 wherein, said dosage is between approximately 3 microliters and approximately 9 microliters.
 3. A microdrop comprising: a ball of liquid enclosing a ball of air.
 4. The microdrop according to claim 3 wherein, the quantity of said liquid is between approximately 3 microliters to approximately 9 microliters.
 5. A microdrop comprising: one thin liquid wall comprising; an exterior portion composing a bubble continuous with an interior portion composing a plurality of closed compartments; each said compartment encloses therein, a gas wherein, the quantity of said liquid is between approximately 3 microliters to approximately 9 microliters of a liquid.
 6. A microdrop comprising: a ball of liquid enclosing at least 2 compartments wherein, each said compartment encloses a gas.
 7. The microdrop according to claim 6 wherein, the quantity of said liquid is between approximately 3 microliters and approximately 9 microliters. 